News — LOS ANGELES (Oct. 23, 2024) -- Cedars-Sinai and UCLA investigators studied first trimester placental tissue and found that for some genes, the process that turns their information into a biological function may depend on the sex of the fetus.
The findings, published in , add to a growing body of research showing the placenta undergoes rapid genetic changes during the first trimester that may have effects lasting into adulthood.
“We know the fetus’ sex can impact a mother’s risk for conditions such as preeclampsia, hyperemesis, and gestational diabetes, as well as risk for miscarriage,” said , director of the Fertility and Reproductive Medicine Center at Cedars-Sinai and corresponding author of the study. “We are trying to understand what exactly happens during sex differentiation that may also affect outcomes for the mother and her baby.”
The investigators studied first trimester placental tissue collected from 56 women who underwent chorionic villus sampling, a prenatal diagnostic test that checks for chromosomal abnormalities and is typically offered to women who will be 35 or older when they give birth. The investigators sought to identify signals that turn genes on and off and how these signals lead to changes in how a gene is expressed.
Many of the genes they identified are on the X and Y chromosomes, which determine sex. (Women have two X chromosomes and men have one X and one Y.) However, the investigators also identified genes expressed on chromosomes that males and females share.
The investigators identified 151 signals that turn genes on and off. The signals affected 18 genes that were turned on or off depending on the sex of the fetus. One gene, for example, ZNF300, was turned on in females but not in males, an observation the investigative team intends to explore further.
In another , Pisarska and colleagues studied placental samples from women in their first and third trimester and observed that sex differences in gene expression were more common in the first trimester.
“The expression of certain genes during early pregnancy may contribute to sex differences in the health and disease of adults,” Pisarska said. “Females, for example, are more likely than males to experience autoimmune diseases. We think gene expressions are markers that define not just pregnancy outcomes, but also tell us how sex differences in certain diseases are manifested.”
The investigators plan to study how modifying which genes get turned on or off might minimize disease in the mother, fetus and eventual child and adult.
Other Cedars-Sinai authors involved in the Biology of Sex Differences study include Tania L. Gonzalez, PhD; Bryn E. Willson, MD; Erica T. Wang; Allynson Novoa, BS; Akhila Swarna, BS; Juanita C. Ortiz; Gianna J. Zeno; Caroline A. Jefferies, PhD; Kate Lawrenson, PhD; John Williams III, MD; Jinrui Cui, MS; and Mark O. Goodarzi, MD, PhD.
This work was supported the National Institutes of Health under awards by the Eunice Kennedy Shriver National Institute of Child Health & Human Development (R01HD091773 to MDP), The National Institute of Allergy and Infectious Disease (R01AI154535 to MDP), the National Institute of Biomedical Imaging and Bioengineering (U01EB026421 to MDP), and the Training Program in Endocrinology, Diabetes, and Metabolism (T32DK007770 to TLG). Infrastructure for the CHARGE Consortium is supported in part by the National Heart, Lung, and Blood Institute (NHLBI) grant R01HL105756. This study was also supported by the National Center for Advancing Translational Sciences, CTSI grant UL1TR001881, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center.
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